Irreversible Damages In Mitochondrial Bioenergetic Of Adriamycin Resistant K562 Cells.
M. Denis-Gay, J.M. Petit, M.H. Ratinaud*, Faculté des Sciences, 87060 LIMOGES Cédex-FRANCE.
The incorporation of Rhodamine 123, a mitochondrial potential dependent probe, in adriamycin-resistant K562 cells seems not really drive by the proton-motive force. Indeed, the slight dye uptake in two variant K562 cells (R 0.2 and R 0.5) occured quasi-independently of temperature. After washing, the cell dye retention was lower in two variants than in sensitive-K562 cells, and was not completely restored by addition of verapamil. Microscopic observations after Rh123 staining showed a bright fluorescence located in mitochondria for sensitive K562 cells, while in resistant cells a weak fluorescence was observed in cytoplasm.
Therefore, biochemical investigations were carried out to study mitochondrial bioenergetic in K562 cells. Differences were observed between cycling cells and quiescent cell lines and more particularly for cytochrome c oxidase activity in K562/R 0.5 cells. The stability of phenomenon during several subcultures without drug suggested a mutation in DNA (mitochondrial or nuclear) due to of adriamycin resistance phenotype acquisition by K562 cells.